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Effects of medium components in a glycerol-based medium on vitamin K (menaquinone-7) production by Bacillus subtilis natto in biofilm reactors

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Abstract

Menaquinone-7 (MK-7) as the most important form of Vitamin K has been reported to have miraculous benefits such as preventing cardiovascular diseases and osteoporosis along with antitumor effects. Therefore, there have been numerous studies in the past decades to improve MK-7 production via microbial fermentation. Unfortunately, both solid and liquid state fermentation strategies that are utilized for MK-7 production, face fundamental operational and scale-up issues as well as intense heat and mass transfer problems during fermentation. In this regard, biofilm reactors seem to be a practical solution to overcome these issues and enhance the production in agitated liquid fermentation. Therefore, this study was undertaken to utilize biofilm reactors in investigating and optimizing different media components in a glycerol-based medium. Using response surface methodology, the effects of glycerol, yeast extract, and soytone were studied in the fermentation medium on MK-7 production in biofilm reactor. With a composition of 48.2 g/L of glycerol, 8.1 g/L of yeast extracts, 13.6 g/L of soytone and 0.06 g/L of K2HPO4, MK-7 concentrations could reach 14.7 ± 1.4 mg/L in biofilm reactors, which was 57% higher compared to the MK-7 concentration achieved in suspended-cell reactors under similar conditions, while glycerol was depleted by the end of the fifth day in biofilm reactors, but glycerol was never depleted in suspended-cell reactors. Evidently, biofilm reactors present a reliable strategy to address the operational issues that occur during MK-7 biosynthesis on an industrial scale production.

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References

  1. Dam H (1935) The antihaemorrhagic vitamin of the chick: occurrence and chemical nature. Nature 135:652–653

    Article  CAS  Google Scholar 

  2. Widhalm JR, Ducluzeau A-L, Buller NE, Elowsky CG, Olsen LJ, Basset GJC (2012) Phylloquinone (vitamin K1) biosynthesis in plants: two peroxisomal thioesterases of Lactobacillales origin hydrolyze 1,4-dihydroxy-2-naphthoyl-CoA. Plant J 71:205–215. https://doi.org/10.1111/j.1365-313X.2012.04972.x

    Article  CAS  PubMed  Google Scholar 

  3. Booth SL (2012) Vitamin K: food composition and dietary intakes. Food Nutr Res 56(1):5505. https://doi.org/10.3402/fnr.v56i0.5505

    Article  CAS  Google Scholar 

  4. Binkley SB, Maccorquodale DW, Thayer A, Doisy EA (1939) The isolation of vitamin K1. J Biol Chem 130:219–234

    CAS  Google Scholar 

  5. Mahdinia E, Demirci A, Berenjian A (2017) Production and application of menaquinone-7 (vitamin K2): a new perspective. World J Microbiol Biotechnol 33:2. https://doi.org/10.1007/s11274-016-2169-2

    Article  CAS  PubMed  Google Scholar 

  6. Schurgers LJ, Teunissen KJF, Hamulyák K, Knapen MHJ, Vik H, Vermeer C (2007) Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood 109:3279–3283. https://doi.org/10.1182/blood-2006-08-040709

    Article  CAS  PubMed  Google Scholar 

  7. Howard LM, Payne AG (2006) Health benefits of vitamin K2: a revolutionary natural treatment for heart disease and bone loss, 1st edn. Basic Health Publications, Inc., Laguna Beach

    Google Scholar 

  8. Gast GCM, de Roos NM, Sluijs I, Bots ML, Beulens JWJ, Geleijnse JM, Witteman JC, Grobbee DE, Peeters PHM, van der Schouw YT (2009) A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Dis 19:504–510. https://doi.org/10.1016/j.numecd.2008.10.004

    Article  CAS  PubMed  Google Scholar 

  9. Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MHJ, van der Meer IM, Hofman A, Witteman JCM (2004) Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam study. J Nutr 134:3100–3105

    Article  CAS  PubMed  Google Scholar 

  10. Yamaguchi M (2006) Regulatory mechanism of food factors in bone metabolism and prevention of osteoporosis. Yakugaku Zasshi 126:1117–1137. https://doi.org/10.1248/yakushi.126.1117

    Article  CAS  PubMed  Google Scholar 

  11. Davidson RT, Foley AL, Engelke JA, Suttie JW (1998) Conversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria. J Nutr 128:220–223

    Article  CAS  PubMed  Google Scholar 

  12. Walther B, Chollet M (2017) Menaquinones, bacteria, and foods: vitamin K2 in the diet. In: Vitamin K2—vital for health and wellbeing. IntechOpen, London, UK, pp 63–82. https://doi.org/10.5772/63712

  13. Berenjian A, Mahanama R, Kavanagh J, Dehghani F (2015) Vitamin K series: current status and future prospects. Crit Rev Biotechnol 35:199–208. https://doi.org/10.3109/07388551.2013.832142

    Article  CAS  PubMed  Google Scholar 

  14. Berenjian A, Mahanama R, Talbot A, Biffin R, Regtop H, Kavanagh J (2011) The effect of amino-acids and glycerol addition on MK-7 production. In: Proc. world congr. eng. comput. sci. II, pp 19–21

  15. Goodman SR, Marrs BL, Narconis RJ, Olson RE (1976) Isolation and description of a menaquinone mutant from Bacillus licheniformis. J Bacteriol 125:282–289

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Wu W-J, Ahn B-Y (2011) Improved menaquinone (vitamin K2) production in cheonggukjang by optimization of the fermentation conditions. Food Sci Biotechnol 20:1585–1591. https://doi.org/10.1007/s10068-011-0219-y

    Article  CAS  Google Scholar 

  17. Singh R, Puri A, Panda BP (2015) Development of menaquinone-7 enriched nutraceutical: inside into medium engineering and process modeling. J Food Sci Technol 52:5212–5219. https://doi.org/10.1007/s13197-014-1600-7

    Article  CAS  PubMed  Google Scholar 

  18. Pandey A (2003) Solid-state fermentation. Biochem Eng J 13:81–84. https://doi.org/10.1016/S1369-703X(02)00121-3

    Article  CAS  Google Scholar 

  19. Ikeda H, Doi Y (1990) A vitamin-K2-binding factor secreted from Bacillus subtilis. Eur J Biochem 192:219–224. https://doi.org/10.1111/j.1432-1033.1990.tb19218.x

    Article  CAS  PubMed  Google Scholar 

  20. Kuchma SL, O’Toole GA (2000) Surface-induced and biofilm-induced changes in gene expression. Curr Opin Biotechnol 11:429–433. https://doi.org/10.1016/S0958-1669(00)00123-3

    Article  CAS  PubMed  Google Scholar 

  21. Mahdinia E, Demirci A, Berenjian A (2017) Strain and plastic composite support (PCS) selection for vitamin K (menaquinone-7) production in biofilm reactors. Bioprocess Biosyst Eng 40:1507–1517. https://doi.org/10.1007/s00449-017-1807-x

    Article  CAS  PubMed  Google Scholar 

  22. Demirci A, Pongtharangkul T, Pometto IIIAL (2007) Applications of biofilm reactors for production of value-added products by microbial fermentation. Blackwell Publishing and The Institude of Food Technologists, Iowa

    Google Scholar 

  23. Ercan D, Demirci A (2013) Production of human lysozyme in biofilm reactor and optimization of growth parameters of Kluyveromyces lactis K7. Appl Microbiol Biotechnol 97:6211–6221. https://doi.org/10.1007/s00253-013-4944-4

    Article  CAS  PubMed  Google Scholar 

  24. Izmirlioglu G, Demirci A (2016) Ethanol production in biofilm reactors from potato waste hydrolysate and optimization of growth parameters for Saccharomyces cerevisiae. Fuel 181:643–651. https://doi.org/10.1016/j.fuel.2016.05.047

    Article  CAS  Google Scholar 

  25. Ho KG, Pometto ALI, Hinz PN, Dickson JS, Demirci A (1997) Ingredient selection for plastic composite supports for l-(1)-lactic acid biofilm fermentation by Lactobacillus casei subsp. rhamnosus. Appl Environ Microbiol 63:2516–2523

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Khiyami MA, Pometto AL, Kennedy WJ (2006) Ligninolytic enzyme production by Phanerochaete chrysosporium in plastic composite support biofilm stirred tank bioreactors. J Agric Food Chem 54:1693–1698. https://doi.org/10.1021/jf051424l

    Article  CAS  PubMed  Google Scholar 

  27. Mahdinia E, Demirci A, Berenjian A (2018) Optimization of Bacillus subtilis natto growth parameters in glycerol-based medium for vitamin K (menaquinone-7) production in biofilm reactors. Bioprocess Biosyst Eng 41:195–204. https://doi.org/10.1007/s00449-017-1857-0

    Article  CAS  PubMed  Google Scholar 

  28. Berenjian A, Mahanama R, Talbot A, Biffin R, Regtop H, Valtchev P, Kavanagh J, Dehghani F (2011) Efficient media for high menaquinone-7 production: response surface methodology approach. N Biotechnol 28:665–672. https://doi.org/10.1016/j.nbt.2011.07.007

    Article  CAS  PubMed  Google Scholar 

  29. Sato T, Yamada Y, Ohtani Y, Mitsui N, Murasawa H, Araki S (2001) Production of menaquinone (vitamin K2)-7 by Bacillus subtilis. J Biosci Bioeng 91:16–20. https://doi.org/10.1016/S1389-1723(01)80104-3

    Article  CAS  PubMed  Google Scholar 

  30. Berenjian A, Mahanama R, Talbot A, Regtop H, Kavanagh J, Dehghani F (2012) Advances in menaquinone-7 production by Bacillus subtilis natto: fed-batch glycerol addition. Am J Biochem Biotechnol 8:105–110. https://doi.org/10.3844/ajbbsp.2012.105.110

    Article  CAS  Google Scholar 

  31. Berenjian A, Chan NL-C, Mahanama R, Talbot A, Regtop H, Kavanagh J, Dehghani F (2013) Effect of biofilm formation by Bacillus subtilis natto on menaquinone-7 biosynthesis. Mol Biotechnol 54:371–378. https://doi.org/10.1007/s12033-012-9576-x

    Article  CAS  PubMed  Google Scholar 

  32. Ercan D, Demirci A (2014) Enhanced human lysozyme production in biofilm reactor by Kluyveromyces lactis K7. Biochem Eng J 92:2–8. https://doi.org/10.1016/j.bej.2014.04.013

    Article  CAS  Google Scholar 

  33. Mahdinia E, Demirci A, Berenjian A (2018) Utilization of glucose-based medium and optimization of Bacillus subtilis natto growth parameters for vitamin K (menaquinone-7) production in bio fi lm reactors. Biocatal Agric Biotechnol 13:219–224. https://doi.org/10.1016/j.bcab.2017.12.009

    Article  Google Scholar 

  34. Shahami M, Ransom R, Shantz DF (2017) Synthesis and characterization of tin, tin/aluminum, and tin/boron containing MFI zeolites containing MFI zeolites. Microporous Misoporous Mater 251:165–172. https://doi.org/10.1016/j.micromeso.2017.05.049

    Article  CAS  Google Scholar 

  35. Rahimi M, Schoener Z, Zhu X, Zhang F, Gorski CA, Logan BE (2017) Removal of copper from water using a thermally regenerative electrodeposition battery. J Hazard Mater 322:551–556. https://doi.org/10.1016/j.jhazmat.2016.10.022

    Article  CAS  PubMed  Google Scholar 

  36. Rahimi M, Angelo AD, Gorski CA, Scialdone O, Logan BE (2017) Electrical power production from low-grade waste heat using a thermally regenerative ethylenediamine battery. J Power Sources 351:45–50. https://doi.org/10.1016/j.jpowsour.2017.03.074

    Article  CAS  Google Scholar 

  37. Fisher SH (1999) MicroReview regulation of nitrogen metabolism in Bacillus subtilis. Mol Microbiol 32:223–232. https://doi.org/10.1046/j.1365-2958.1999.01333.x

    Article  CAS  PubMed  Google Scholar 

  38. Ashby RD (2005) Synthesis of short-/medium-chain-length poly(hydroxyalkanoate) blends by mixed culture fermentation of glycerol. Biomacromol 6:2106–2112. https://doi.org/10.1021/bm058005h

    Article  CAS  Google Scholar 

  39. Nishikawa M, Ogawa K (2006) Inhibition of epsilon-poly-l-lysine biosynthesis in Streptomycetaceae bacteria by short-chain polyols. Appl Environ Microbiol 72:2306–2312. https://doi.org/10.1128/AEM.72.4.2306-2312.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Qureshi N, Annous BA, Ezeji TC, Karcher P, Maddox IS (2005) Biofilm reactors for industrial bioconversion processes: employing potential of enhanced reaction rates. Microb Cell Fact 4(1):24. https://doi.org/10.1186/1475-2859-4-24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Mahdinia E, Demirci A, Berenjian A (2018) Implementation of fed-batch strategies for vitamin K (menaquinone-7) production by Bacillus subtilis natto in biofilm reactors. Appl Microbiol Biotechnol 102(21):9147–9157. https://doi.org/10.1007/s00253-018-9340-7

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the USDA National Institute of Food and Agriculture Federal Appropriations under Project PEN04561 and Accession number 1002249. The authors thank the Statistical Consulting Center at The Pennsylvania State University for their support in providing useful consultation for data processing.

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Correspondence to Ali Demirci.

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Mahdinia, E., Demirci, A. & Berenjian, A. Effects of medium components in a glycerol-based medium on vitamin K (menaquinone-7) production by Bacillus subtilis natto in biofilm reactors. Bioprocess Biosyst Eng 42, 223–232 (2019). https://doi.org/10.1007/s00449-018-2027-8

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